1. Field of the Invention
The present invention related to a new process for the preparation of the compounds of the formula 1 (where R1 and R2 represent C1-C4 alkyl group) and their hydrochloride thereof, and other various pharmaceutical used salts. The process is more efficient than the reported processes in total yield and reaction steps for the synthesis of compounds having the formula 1. In the present invention, the use of optically pure starting material can provide the desired compound in more specific range to meet the pharmaceutical requirement. Furthermore, the shorter reaction steps will provide the desired drugs with limit scope of impurity profile.

2. Description of the Prior Art
It is described in the U.S. Pat. No. 5,447,958 that the compounds of the above formula 1 have excellent therapeutic effects against hypertension, congestive heart failure, angina pectoris or prostatic hypertrophy. In addition, the above patent disclosed a process for the preparation of compounds with the formula 1 by reacting following hydrochlorides of sulfonamide 2A with bromide 3:

Wherein, sulfonamide hydrochloride salt 2B (hydrochloride of formula 2A) can be synthesized from the Process 1 depicted below. The synthetic procedure of Process 1 involves phenylamine 4A as the starting material to produce the intermediates of acetamide 5A and (sulfo)acetamide 6A, and then to give sulfonamide hydrochloride salt 2B.
Process 1:

The synthesis of phenylamine 4A was disclosed in U.S. Pat. No. 4,000,197 and J. Med. Chem. 1973, 16, 480-483 by condensation of 4-methoxyphenylacetone with (R)-α-methylbenzylamine, followed by hydrogenation of the N═N double bond therein, and reductive debenzylation. The total yield for the preparation of phenylamine 4A is 25% with >99% enantiomeric purity.
Yamada et al. described a process for the synthesis of phenylamine 4A in Synth. Commun. 1998, 28, 1935-1945 by using optically pure L-tyrosine as the starting material. The advantage of the current process is that the resultant product is optically pure. The preparation of intermediate 4B (hydrochloride of phenylamine 4A) involves overall 8 steps, and if extended to intermediate 5A, would be 9 steps. Yamada's procedure is depicted in Process 2 as below:
Process 2:

The synthetic procedure of Process 2 uses L-tyrosine 7 as the starting material to generate the intermediates of aminoester 8, (phenol)amidoester 9, (ether)amidoester 10, (hydroxy)ether amide 11, tosyl amide 12, iodide 13, ether amide 14, and finally to obtain hydrochloride of phenylamine 4B.